The blood coagulation factor XIII (FXIII), the fibrin stabilising factor, is a transglutaminase that binds to and cross-links fibrin monomers in the haemostatic plug thereby providing a fibrin structure with increased mechanical strength and resistance against fibrinolysis (see Ariëns et al, Blood 100(3), 743-754 (2002)). Factor XIII is also known as “fibrinoligase” and “fibrin stabilizing factor”. When activated, factor XIIIa is able to form intermolecular gamma-glutamyl-ε-lysine cross-links between side chains of fibrin molecules and other substrates. Factor XIII is found in plasma and in platelets. The enzyme exists in plasma as a tetrameric zymogen consisting of two A-subunits (also referred to as “a”) and two B subunits (also referred to as “b”) (this tetrameric zymogen is designated A2B2 (also referred to as “a2b2”)) and in platelets as a zymogen consisting of two A-subunits (this dimeric zymogen is designated A2-dimer (also referred to as “a2-dimer”)).
It has been described that factor XIII may be used for treating bleeding episodes, in patients having a congenital factor XIII deficiency as well as in patients not having a congenital factor XIII deficiency, see for instance U.S. Pat. No. 5,114,916, U.S. Pat. No. 5,607,917, WO 2002038167, WO 2002036155, WO 200267981, and WO 200267980.
U.S. Pat. No. 5,612,456 concerns the preparation of factor XIII from biological fluids using an acetate precipitation step in combination with anion-exchange chromatography and hydrophobic interaction chromatography.